We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (MM)

This study is currently recruiting participants.
Verified October 2017 by AbbVie
Sponsor:
ClinicalTrials.gov Identifier:
NCT02899052
First Posted: September 14, 2016
Last Update Posted: November 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Genentech, Inc.
Onyx Therapeutics, Inc.
Information provided by (Responsible Party):
AbbVie
September 1, 2016
September 14, 2016
November 2, 2017
January 19, 2017
March 27, 2020   (Final data collection date for primary outcome measure)
Adverse events [ Time Frame: First dose of study drug through at least 30 days after end of treatment (approximately 2 years) ]
Same as current
Complete list of historical versions of study NCT02899052 on ClinicalTrials.gov Archive Site
  • Objective response rate (ORR) in participants with relapsed or refractory MM and in a subset of participants with high B-cell lymphocyte-2 (BCL-2) expression [ Time Frame: Up to approximately 17 months ]
    ORR is defined as the proportion of participants with documented partial response (PR) or better based on International Myeloma Working Group (IMWG) criteria.
  • Very Good Partial Response (VGPR) or better response rate in participants with relapsed or refractory MM and in a subset of participants with high BCL-2 expression [ Time Frame: Up to approximately 17 months ]
    VGPR or better response rate is defined as the proportion of participants with documented VGPR or better based on IMWG criteria.
  • Progression-free survival (PFS) in participants with relapsed or refractory MM and in a subset of participants with high BCL-2 expression [ Time Frame: Up to approximately 17 months ]
    PFS is defined as the number of days from the date of the first dose of study drug to the date of the first documented progressive disease (PD) or death due to any cause, whichever occurs first.
  • Time to progression (TTP) in participants with relapsed or refractory MM and in a subset of participants with high BCL-2 expression [ Time Frame: Up to approximately 17 months ]
    TTP is defined as the number of days from the date of the first dose of study drug to the date of first documented PD or death due to MM, whichever occurs first.
  • Duration of overall response (DOR) in participants with relapsed or refractory MM and in a subset of participants with high BCL-2 expression [ Time Frame: Up to approximately 17 months ]
    DOR is defined as the number of days from the participant's date of first documented response (PR or better) to the date of first documented PD or death due to MM, whichever occurs first.
  • Minimal residual disease (MRD) [ Time Frame: Up to 2 years (Screening, Cycle 3 Day 1, and Confirmation of Stringent Complete Response [sCR]/Complete Response [CR]) ]
    MRD in the bone marrow by next generation sequencing.
  • Maximum plasma concentration (Cmax) of venetoclax [ Time Frame: Approximately 24 hours post-dose on Cycle 1 Days 1 and 15 ]
  • Time to maximum plasma concentration (peak time, Tmax) of venetoclax [ Time Frame: Approximately 24 hours post-dose on Cycle 1 Days 1 and 15 ]
  • Area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) post-dose of venetoclax [ Time Frame: Approximately 24 hours post-dose on Cycle 1 Days 1 and 15 ]
  • Cmax of carfilzomib [ Time Frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 ]
  • Terminal phase elimination rate constant (β) of carfilzomib [ Time Frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 ]
  • Terminal elimination half-life (t1/2) of carfilzomib [ Time Frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 ]
  • AUC from time 0 to the time of the last measurable concentration (AUCt) of carfilzomib [ Time Frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 ]
  • AUC from 0 to infinity (AUC∞)of carfilzomib [ Time Frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 ]
  • Clearance (CL) of carfilzomib [ Time Frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 ]
Same as current
Not Provided
Not Provided
 
Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (MM)
A Phase 2, Open-Label, Multi-Center Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
A Phase 2, open-label, dose escalation study to evaluate the safety and efficacy of venetoclax in combination with carfilzomib-dexamethasone (Kd) in participants with relapsed or refractory MM and have received 1 to 3 prior lines of therapy.
Not Provided
Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Relapsed or Refractory Multiple Myeloma
  • Drug: Venetoclax
    Venetoclax tablet administered orally once daily during Cycles 1-18. Venetoclax dose level 1 (Ven1) 400 mg once daily, Ven2 800 mg once daily.
    Other Name: ABT-199
  • Drug: Dexamethasone
    Dexamethasone tablet administered orally during Cycles 1 - 18. Dexamethasone dose level 1 (Dex1) 40 mg once weekly, Dex2 40 mg once weekly, Dex3 20 mg twice weekly.
  • Drug: Carfilzomib

    Carfilzomib lyophilized administered intravenously as a 10 to 30 minute infusion in Cycles 1 - 18 within 30 minutes to 4 hours after dexamethasone dosing.

    Dose level 1 (K1) Cycle 1: 20 mg/m2 on Days 1 and 2, 27 mg/m2 on Days 8, 9, 15, and 16; Cycles 2 - 12: 27 mg/m2 on Days 1, 2, 8, 9, 15, and 16; Cycles 13 - 18: 27 mg/m2 on Days 1, 2, 15, and 16.

    Dose Level K2: Cycle 1: 20 mg/m2 on Day 1; 70 mg/m2 on Days 8 and 15 Cycles 2 - 18: 70 mg/m2 on Days 1, 8, and 15. Dose Level K3: Cycle 1: 2 mg/m2 on Days 1 and 2; 56 mg/m2 on Days 8, 9, 15, and 16.

    Cycles 2 - 18: 56 mg/m2 on Days 1, 2, 8, 9, 15, and 16.

    Other Name: Kyprolis
Experimental: Venetoclax + Carfilzomib + Dexamethasone
Part 1: Evaluate the safety and pharmacokinetic profiles while providing information to determine the appropriate doses of venetoclax and carfilzomib (VenKd) to be used in the VenKd combination in approximately 9-18 subjects. The dose levels are Venetoclax 400 mg or 800 mg; Carfilzomib 20/27 mg/m2, 20/70 mg/m2, and/or 20/56 mg/m2; Dexamethasone 40 mg Part 2: Further evaluate the safety and efficacy profile of the VenKd combination selected after completion of Part 1 in approximately 22 - 31 additional subjects. Participants may discontinue Kd but may continue receiving venetoclax once daily (QD) as monotherapy.
Interventions:
  • Drug: Venetoclax
  • Drug: Dexamethasone
  • Drug: Carfilzomib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
40
December 22, 2020
March 27, 2020   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Eastern Collaborative Oncology Group (ECOG) performance score of less than or equal to 2.
  • Documented relapsed or progressive Multiple Myeloma (MM) on or after any regimen or is refractory to the most recent line of therapy.
  • Received prior treatment with at least 1, but no more than 3, prior lines of therapy for MM.
  • Measurable disease on Screening per International Myeloma Working Group (IMWG) criteria.
  • Meets absolute neutrophil count, platelet count, hemoglobin, liver and kidney function laboratory values within 2 weeks prior to first dose of study drug.

Exclusion Criteria:

  • Has a pre-existing condition that is contraindicated including
  • Non-secretory or oligo-secretory MM
  • Active plasma cell leukemia
  • Waldenström's macroglobulinemia
  • Primary amyloidosis
  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  • Active hepatitis B or C infection based on screening blood testing
  • Significant cardiovascular disease
  • Major surgery within 4 weeks prior to first dose
  • Acute infections requiring parenteral therapy
  • Peripheral neuropathy ≥ Grade 3 or ≥ Grade 2 with pain within 2 weeks prior to first dose
  • Uncontrolled diabetes or uncontrolled hypertension within 14 days prior to first dose
  • Any other medical condition that, in the opinion of the Investigator, would adversely affect the subject's participation in the study.
  • History of other active malignancies, including myelodysplastic syndrome (MDS), within the past 3 years prior to study entry Other protocol defined inclusion/exclusion criteria could apply
Sexes Eligible for Study: All
18 Years to 99 Years   (Adult, Senior)
No
Contact: AbbVie_Call Center 847-283-8955 abbvieclinicaltrials@abbvie.com
Puerto Rico,   United States
 
 
NCT02899052
M15-538
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
AbbVie
AbbVie
  • Genentech, Inc.
  • Onyx Therapeutics, Inc.
Principal Investigator: Orlando Bueno, MD AbbVie
AbbVie
October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP